Abstract
Spondylocostal dysostosis (SCDO) is a heterogeneous group of skeletal disorders characterized by multiple segmentation defects involving vertebrae and ribs. Seven disease genes have been reported as causal genes for SCDO: DLL3, MESP2, TBX6, HES7, RIPPLY2, DMRT2, and LFNG. Here we report a Japanese SCDO case with multiple severe vertebral anomalies from cervical to sacral spine. The patient was a compound heterozygote for c.372delG (p.K124Nfs*) and c.601G>A (p.D201N) variants of LFNG, which encodes a glycosyltransferase (O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase). The missense variant was in the DxD motif, an active-site motif of the glycosyltransferase, and its loss of the enzyme function was confirmed by an in vitro enzyme assay. This is the second report of LFNG mutations in SCDO.
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Acknowledgements
This study was supported by research grants from the Japan Orthopaedics and Traumatology Foundation (for NO. and KT), Japan Agency For Medical Research and Development (AMED) (contract Nos. 17ek0109212h0001 and 17ek0109280h0001 for SI), the Japan Society for the Promotion of Science (WAKATE B, No. 17K16710 for LG), the Cooperative Research Program (Joint Usage/Research Center program) of Institute for Frontier Life and Medical Sciences, Kyoto University (for SI and LG), and the Japan Society for the Promotion of Science (for SM., No. 16K08251).
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Otomo, N., Mizumoto, S., Lu, HF. et al. Identification of novel LFNG mutations in spondylocostal dysostosis. J Hum Genet 64, 261–264 (2019). https://doi.org/10.1038/s10038-018-0548-2
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DOI: https://doi.org/10.1038/s10038-018-0548-2
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